Clinical Immunology of the Dog and Cat

449 Pages·2008·37.278 MB·English

by  Thomas K. Day

CLINICAL
IMMUNOLOGY
OF THE
DOG AND CAT
Second Edition
Michael J Day
BSc BVMS (Hons) PhD DSc DiplECVP FASM FRCPath FRCVS
Professor of Veterinary Pathology
Langford, Bristol, UK

Manson Publishing/The Veterinary Press
http://avaxhome.ws/blogs/ChrisRedfield
Dedication
To Lara, Christopher and Natalie
Disclaimer
The authors and Publisher have made every effort to ensure that therapeutic recommendations
(particularly those concerning immunomodulatory and cytotoxic drug selection and dosage) set out
in the text are in accord with current recommendations and practice. However, in view of ongoing
research, changes in government regulations and the constant flow of information relating to drug
therapy and drug reactions, the reader is urged to check the package insert for any added warnings
and precautions.
The cytotoxic drugs detailed in this book are not licensed for veterinary use. All of these agents
are potentially hazardous to the patient and to persons handling or administering them. Veterinary
surgeons who prescribe such drugs to patients in their care must assume responsibility for their use
and safe handling. Veterinary surgeons who are not familiar with the use of cytotoxic agents should
seek further information and advice from a specialist.
Copyright © 2008 Manson Publishing Ltd
ISBN: 978-1-84076-098-9
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or
transmitted in any form or by any means without the written permission of the copyright holder or
in accordance with the provisions of the Copyright Act 1956 (as amended), or under the terms of
any licence permitting limited copying issued by the Copyright Licensing Agency, 33–34 Alfred
Place, London WC1E 7DP, UK.
Any person who does any unauthorized act in relation to this publication may be liable to criminal
prosecution and civil claims for damages.
A CIP catalogue record for this book is available from the British Library.
For full details of all Manson Publishing Ltd titles please write to:
Manson Publishing Ltd, 73 Corringham Road, London NW11 7DL, UK.
Tel: [phone]
Fax: [phone]
Email: [email protected]
Website: www.mansonpublishing.com
Commissioning editor: Jill Northcott
Project manager: Paul Bennett
Copy editor: Peter Beynon
Layout: DiacriTech, Chennai, India
Colour reproduction: Tenon & Polert Colour Scanning Ltd, Hong Kong
Printed by: Grafos SA, Barcelona, Spain
CONTENTS
Preface (First Edition) 6 3 The Basis of Immune-Mediated Disease 75
M. J. Day
Preface (Second Edition) 7 The spectrum and interrelationship
of immune-mediated disease 75
Contributors 8 Immunological mechanisms underlying
allergic disease 76
Abbreviations 8 Immunological mechanisms underlying
autoimmune disease 78
Key to Symbols 10 Genetic defects underlying
immunodeficiency disease 88
1 Basic Immunology 11 The induction of lymphoid neoplasia 88
M. J. Day Major histocompatibility complex and
Introduction 11 other genetic associations with
The immune system: an overview 11 immune-mediated disease 90
Antigens 12 Further reading 93
Antibodies (immunoglobulins) 14
Antigen–antibody interactions 16 4 Immune-Mediated Haematological Disease 94
Complement 16 M. J. Day and A. J. Mackin
Cells of the immune system 21 Introduction 94
Tissues of the immune system 29 Immune-mediated haemolytic anaemia
Lymphocyte recirculation 34 in the dog 94
The major histocompatibility complex 36 Immune-mediated haemolytic anaemia
Cytokines 39 in the cat 106
T lymphocytes 41 Immune-mediated thrombocytopenia
B lymphocytes 45 in the dog 108
Antigen presentation 46 Immune-mediated thrombocytopenia
T lymphocyte activation 50 in the cat 114
B lymphocyte activation 52 Cold agglutinin disease 115
Cytotoxicity 53 Immune-mediated neutropenia
Immunoregulation 54 in the dog 115
Immunological memory 57 Feline blood group antigens 115
Immunological tolerance 58 Canine blood group antigens 116
Age-related changes in the immune system 58 Blood transfusion reactions 117
Further reading 59 Blood transfusion protocol 119
Neonatal isoerythrolysis 119
2 Immunopathological Mechanisms 61 Further reading 120
M. J. Day
Introduction 61 5 Immune-Mediated Skin Disease 122
Type I hypersensitivity 62 M. J. Day and S. E. Shaw
Type II hypersensitivity 66 Introduction 122
Type III hypersensitivity 67 Cutaneous disease caused by type I
Type IV hypersensitivity 69 hypersensitivity 124
Superantigens 73 Contact hypersensitivity 142
Amyloidosis 73 Cutaneous vasculitis 145
Further reading 74 Pemphigus and bullous pemphigoid 148
CONTENTS
Cutaneous lupus erythematosus 157 9 Immune-Mediated Endocrine Disease 241
Dermatomyositis 160 M. J. Day and S. E. Shaw
Dermatouveitis 162 Introduction 241
Erythema multiforme and toxic Canine hypothyroidism 241
epidermal necrolysis 162 Feline hyperthyroidism 246
Sebaceous adenitis 165 Lymphocytic parathyroiditis 246
Alopecia areata 166 Diabetes mellitus 247
Pseudopelade 167 Hypoadrenocorticism 249
Canine granulomatous mural folliculitis 168 Polyendocrine disease 250
Plasma cell pododermatitis 168 Further reading 250
Feline atrophic auricular polychondritis 169
Further reading 170 10 Immune-Mediated Urinary and
Reproductive Disease 251
6 Immune-Mediated Musculoskeletal and M. J. Day and A. J. Mackin
Neurological Disease 172 Introduction 251
M. J. Day and D. Bennett Immune complex glomerulonephritis 251
Introduction 172 Glomerular basement membrane
Immune-mediated polyarthritis 172 autoimmunity 259
Myositis 190 Chronic interstitial nephritis 259
Myasthenia gravis 193 Reproductive immunology 260
Polyneuritis 195 Further reading 262
Degenerative myelopathy of German
Shepherd Dogs 196 11 Immune-Mediated Ocular Disease 263
Granulomatous meningoencephalitis 197 M. J. Day and S. M. Crispin
Necrotizing meningoencephalitis 197 Ocular immunity 263
Necrotizing leukoencephalitis 197 Immune-mediated conjunctival disease 264
Greyhound meningoencephalitis 198 Immune-mediated diseases of the
Polyarteritis nodosa 198 cornea 270
Steroid-responsive meningitis–arteritis 199 Immune-mediated diseases of the uvea 275
Further reading 199 Immune-mediated diseases of the
canine retina 281
7 Immune-Mediated Alimentary Disease 201 Immune-mediated diseases of the
M. J. Day and E. J. Hall canine sclera and episclera 282
Gastrointestinal immunology 201 Further reading 286
Immune-mediated gastrointestinal
disease 204 12 Immunodeficiency Disease 287
Immune-mediated hepatic disease 221 M. J. Day
Immune-mediated disease of the Introduction 287
exocrine pancreas 225 Secondary immunodeficiency 287
Further reading 225 Primary immunodeficiency 291
Therapy for immunodeficiency disease 313
8 Immune-Mediated Respiratory and Further reading 313
Cardiac Disease 228
M. J. Day and C. Clercx
The respiratory immune system 228
Immune-mediated respiratory disease 230
Immune-mediated cardiac disease 238
Further reading 239
4
CONTENTS
13 Immune System Neoplasia 315 16 Immunotherapy 391
M. J. Day and J. M. Dobson M. J. Day
Introduction 315 Introduction 391
Lymphoma 318 Immunomodulatory drugs 391
Lymphomatoid granulomatosis 337 Monoclonal antibodies in
Lymphoid leukaemia 338 immunotherapy 398
Multiple myeloma 339 Antigen-specific immunotherapy 403
Waldenström’s macroglobulinemia 342 Gene therapy 407
Plasmacytoma 342 Transplantation and stem cell therapy 408
Myeloproliferative disease 342 Further reading 411
Histiocytoma 344
Cutaneous and systemic histiocytosis 346 17 Vaccination 413
Histiocytic sarcoma 346 M. J. Day
Mast cell tumour 349 Introduction 413
Systemic mastocytosis 354 The aim of vaccination 413
Further reading 354 Basic requirements of a vaccine 413
Types of vaccine 413
14 Multisystem and Intercurrent Immune- Vaccines of the future 418
Mediated Disease 356 Duration of immunity 420
M. J. Day Vaccine licensing 423
Introduction 356 Adverse effects of vaccination 424
Systemic lupus erythematosus 356 Vaccine guidelines 429
Autoimmunity and lymphoma 363 Further reading 430
Myasthenia gravis and thymoma 364
IgA deficiency, hypersensitivity and Glossary 432
autoimmunity 367
Further reading 368 Index 442
15 Diseases of Lymphoid Tissue 369
M. J. Day
Introduction 369
Diseases of the thymus 369
Lymph node diseases 374
Diseases of lymphatic vessels 382
Diseases of the tonsil 384
Diseases of the spleen 384
Further reading 390
5
PREFACE
(First Edition)
Clinical Immunology of the Dog and Cat is a many people. I would firstly like to acknowledge
unique textbook that leads the reader from basic the role of my contributors in co-writing a number
immunological principles to their practical of the chapters. These clinical colleagues are each
application in the diagnosis and treatment of internationally recognized leaders within their
immune-mediated diseases of the major companion disciplines, and it has been a pleasure to have the
animal species. The book is primarily designed as a opportunity to work with them. They have
reference source for veterinary surgeons in general generously allowed me to reproduce photographs
or specialist practice who may require easily from their collections and have provided the
accessible and up-to-date information on this majority of information on therapy and manage-
important group of diseases. Sufficient immuno- ment of the disease entities to complement my
logical background is given to make the text of immunopathological observations.
value to veterinarians undertaking residency My colleagues, graduate students and
training or preparation for specialist examination. technicians within the Departments of Pathology
The integrated approach to pathology, clinical and Microbiology and Clinical Veterinary Science
pathology and clinical medicine should also be of at the have generated data and
benefit to veterinary undergraduates. material that have been incorporated into this
The first three chapters of the book summarize book, and I am grateful for their support and for
current knowledge of basic cellular and molecular the departmental infrastructure that has allowed me
mechanisms in this rapidly evolving discipline and the facilities to produce this work. The majority of
describe the multifactorial basis and pathogenesis the colour photographs of clinical cases and gross
of the immune-mediated diseases. The following pathology are the expert products of talented
nine chapters are system-based and describe the medical photographers: Malcolm Parsons, John
immunological basis, clinical signs, diagnostic Conibear and Tracy Townsend-Sweeting (Uni-
procedures, therapy and prognosis for those versity of Bristol) and Geoff Griffiths (Murdoch
immune-mediated disorders of each system that are University).
recognized in the dog and cat. Separate chapters I would like to acknowledge the contribution of
deal with multisystems disease and disorders of Jill Northcott, who originally had the idea for this

lymphoid tissues, and the final chapter provides an text. The finished product has been expertly and
insight into how current research and experimental efficiently created by Manson Publishing, and I am
immunotherapies may be applied to clinical grateful to Michael Manson for his enthusiasm for
veterinary medicine in future years. the book, and to the skilled production team of
One major strength of this work is the use of Paul Bennett (project manager), Peter Beynon (copy
extensive full colour diagrams and photographs. To editor), and Sue Tyler and Kate Nardoni (illus-
enhance understanding, the diagrams utilize a trators), with whom it has been a pleasure to work.
consistent set of symbols for various immunological In writing this preface, it is appropriate that I
cells and molecules, and these are defined in the key have the opportunity to acknowledge my three
that follows. The range of photographic material mentors (Professor John Penhale, Professor Chris
includes examples of clinical cases, radiographs, Elson and Dr. Don Mason), who introduced me to
endoscopy, cytology, gross and microscopic this exciting discipline and shaped my early career
pathology, immunopathology and electron micros- in immunology. Finally, I am grateful for the
copy. The book also contains a list of abbreviations unstinting indulgence of my parents who supported
and a list of selected further reading for each my drawn-out education, and the understanding of
chapter, mostly papers from readily accessible my own family, who tolerated my long hours of
veterinary journals from the past five years. solitary confinement.
Clinical Immunology of the Dog and Cat has
been an exciting project to develop, but it would Michael J. Day
not have been possible without the valued input of
6
PREFACE
(Second Edition)
I was delighted by the success of the first edition of providing updated information on current
Clinical Immunology of the Dog and Cat, which therapeutic aspects of the diseases covered. I was
clearly filled a niche in the veterinary textbook pleased to welcome Professor Cecile Clercx to this
market and was eventually translated into six group of internationally recognized clinical
additional languages. Immunology, however, is specialists, and I thank them all for their insightful
probably the fastest moving of the sciences and, editing of the text.
since the publication of the first edition in 1999, This is now my third publication with Manson
there have been numerous advances that readily Publishing and I am pleased to acknowledge this
justify the production of this second edition. In the continuing relationship. The reputation of this
area of fundamental immunology there has been a small publishing house is founded on the exception-
renewed focus on the importance of the innate ally high standards and quality of printed texts that
immune system, with a realization that events at they produce, and I am grateful to Mike Manson
this level of antigen recognition determine the and Jill Northcott for their expertise in developing
nature of the ensuing adaptive immune response. and marketing projects such as this. Both have also
Additionally, there has been recent clarification of been very patient with the protracted gestation of
the role of regulatory (suppressor) T lymphocytes in this volume, the birth of which was promised some
the immune response and identification of several years before the actual event! I am very pleased to
functional subsets of these cells. In parallel with this acknowledge the team that has worked on this
research has been an explosion of knowledge in the second edition, including Paul Bennett (project
field of companion animal immunology, largely manager), Peter Beynon (copy editor) and Sue Tyler
driven by the molecular revolution, which in turn is and Kate Nardoni (illustrators).
underpinned by publication of the canine (and, Finally, it would be remiss of me not to
soon, the feline) genome. Techniques have been acknowledge the continued patience and support of
developed that have allowed us to explore and my family who, when welcoming visitors to the
quantify the role of key immunological molecules in house, point out ‘that’s the study … where we keep
canine and feline immune responses, and this Dad’.
technology has rapidly translated to the clinical

diagnostic labora tory with the advent of PCR-based Michael J. Day
tests for the diagnosis of infection or detection of
clonality of neoplastic lymphoid populations. These
advances are all discussed within this second
edition.
In order to incorporate these advances in
understanding, by necessity this second edition of
Clinical Immunology of the Dog and Cat has
grown. There is an additional chapter devoted to
respiratory and cardiac disease and, given the
continued focus of companion animal practitioners
on vaccine-related issues, a new chapter is devoted
entirely to the subject of vaccinology. The second
edition also includes approximately 200 new
photographic images, an updated list of further
reading (specifically papers published since the first
edition in 1999), and an extensive glossary of
terms.
As ever, I am indebted to my contributors for
their continued enthusiasm for this book and for
7
CONTRIBUTORS
Professor David Bennett BSc BVetMed PhD ILTM Professor Edward J. HallMA VetMB PhD DipECVIM-
DSAO MRCVS ca MRCVS
Professor of Small Animal Clinical Studies Professor of Small Animal Internal Medicine
Division of Companion Animal Sciences School of Clinical Veterinary Science
Faculty of Veterinary Medicine , Langford, Bristol, UK
University of Glasgow, Glasgow, UK
Professor Andrew J. MackinBSc BVMS MVS DVSc
Professor Cécile Clercx DVMPhD DipECVIM-ca DSAM FACVSc DACVIM MRCVS
Professor of Small Animal Internal Medicine Hugh G. Ward Endowed Chair of Small Animal
Department of Veterinary Clinical Sciences Medicine
Faculty of Veterinary Medicine College of Veterinary Medicine
University of Liège, Liège, Belgium Mississippi State University, Mississippi, USA
Professor Sheila Crispin MA VetMB BSc PhD DVA Dr. Susan E. ShawBVSc MSc FACVSc DipACVIM
DVOphthal DipECVO FRCVS DipECVIM-ca MRCVS
Cold Harbour Farm Senior Lecturer in Veterinary Dermatology
Kendal, Cumbria, UK School of Clinical Veterinary Science
, Langford, Bristol, UK
Dr. Jane M. Dobson MA DVetMed DipECVIM-ca
MRCVS
Senior Lecturer in Veterinary Clinical Oncology
Department of Clinical Veterinary Medicine
University of Cambridge, Cambridge, UK
ABBREVIATIONS
AA amyloid amyloid-associated protein BUN blood urea nitrogen
ACAID anterior chamber-associated immune deviation CALT conjunctiva-associated lymphoid tissue
ACE angiotensin converting enzyme CAV canine adenovirus
AChR acetylcholine receptor CBC complete blood count
AD atopic dermatitis CC a chemokine in which the two amino terminal
ADCC antibody-dependent cell-mediated cytotoxicity cysteine residues are adjacent
AIDS acquired immune deficiency syndrome CD cluster of differentiation
AIEC attaching and invading E. coli CDV canine distemper virus
AIHA autoimmune haemolytic anaemia CGL chronic granulocytic leukaemia
AITP autoimmune thrombocytopenia CH chronic hepatitis
AL amyloid amyloid (immunoglobulin) light chain CH total haemolytic complement (assay)
50
protein CIC circulating immune complex
ALL acute lymphoblastic leukaemia CLAD canine leukocyte adhesion deficiency
AMD acute myeloproliferative disease CLE cutaneous lupus erythematosus
AML acute myeloid leukaemia CLL chronic lymphocytic leukaemia
ANA antinuclear antibody CMD chronic myeloproliferative disease
APC antigen presenting cell CMI cell-mediated immunity
ARD antibiotic responsive diarrhoea CML chronic myeloid leukaemia
ASIT allergen-specific immunotherapy CNS central nervous system
BALF bronchoalveolar lavage fluid ConA concanavalin A (mitogen)
BALT bronchial-associated lymphoid tissue CMMM canine masticatory muscle myositis
BCG bacille Calmette–Guérin CPM canine polymyositis
BLAD bovine leukocyte adhesion deficiency CRFK Crandall Rees feline kidney cell line
BMZ basement membrane zone CR1 complement receptor 1
8
ABBREVIATIONS
CSF cerebrospinal fluid IDDM insulin-dependent diabetes mellitus
CSK/CSKC chronic superficial IDST intradermal skin test
keratitis/keratoconjunctivitis IEL intraepithelial lymphocyte
CT computerized tomography IEP immunoelectrophoresis
CXC a chemokine in which the two amino terminal IFN interferon (e.g. IFN )
cysteine residues are separated by one amino acid Ig immunoglobulin (IgG, IgM, IgA, IgD, IgE)
DAF decay accelerating factor IGF-1 insulin-like growth factor-1
DAMP damage-associated molecular pattern IL interleukin (e.g. IL-1)
DEA dog erythrocyte antigen i/m intramuscular
DGGE denaturing gradient gel electrophoresis IMHA immune-mediated haemolytic anaemia
DIC disseminated intravascular coagulation IMNP immune-mediated neutropenia
DLA dog leukocyte antigen (canine MHC) IMTP immune-mediated thrombocytopenia
DLE discoid lupus erythematosus i/p intraperitoneal
DLH domestic longhair (cat) IPE idiopathic pericardial effusion
DNA deoxyribonucleic acid ITP idiopathic thrombocytopenia
DOI duration of immunity i/v intravenous/intravascular
DOP duration of protection KCS keratoconjunctivitis sicca
DSH domestic shorthair (cat) KIR killer-cell inhibitory factor
DTH delayed-type hypersensitivity LAK lymphokine-activated killer (cells)
EAE experimental allergic encephalomyelitis LFA-1 lymphocyte function-associated
EBP eosinophilic bronchopneumopathy antigen 1
EGC eosinophilic granuloma complex LPC lymphoplasmacytic colitis
ELISA enzyme-linked immunosorbent assay LPE lymphoplasmacytic enteritis
EM erythema multiforme LPL lamina propria lymphocyte
EMG electromyogram LPR lymphoplasmacytic rhinitis
EPEC enteropathogenic Escherichia coli LPS lipopolysaccharide
EPI exocrine pancreatic insufficiency LSEC liver sinusoidal endothelial cell
Fab antigen-binding fragment (of Ig) MAC membrane attack complex
FACS fluorescence-activated cell sorter MAdCAM mucosal addressin cell adhesion molecule
FAD flea allergy dermatitis MALT mucosa-associated lymphoid tissue
Fc crystallizable fragment (of Ig) MBP myelin basic protein
FCV feline calicivirus MCP macrophage chemotactic protein/membrane co-
FcR Fc (Ig heavy chain) receptor factor protein
FeFV feline foamy virus MG myasthenia gravis
FeLV feline leukaemia virus MHC major histocompatibility complex
FHV feline herpesvirus MMP matrix metalloproteinase
FIA feline infectious anaemia MRI magnetic resonance imaging
FIE feline infectious enteritis mRNA messenger RNA
FIP feline infectious peritonitis NALT nasal-associated lymphoid tissue
FIV feline immunodeficiency virus NBT nitroblue tetrazolium (test)
FLA feline leukocyte antigen (feline MHC) NCIWF National Cancer Institute Working Formulation
GALT gut-associated lymphoid tissue NFAT nuclear factor of activated T cells
GBM glomerular basement membrane NK natural killer (cells)
G-CSF granulocyte colony stimulating factor NLE necrotizing leukoencephalitis
GITR glucocorticoid-induced TNF receptor-related gene NME necrotizing meningoencephalitis
GM-CSF granulocyte-macrophage colony stimulating NRIMHA non-regenerative immune-mediated
factor haemolytic anaemia
GME granulomatous meningoencephalitis NSAID non-steroidal anti-inflammatory drug
GP glycoprotein OspA outer surface protein A (of Borrelia burgdorferi)
GSD German Shepherd Dog OVA ovalbumin
HAT hypoxanthine, aminopterin, thymidine (medium) PAA pancreatic acinar atrophy
HEV high endothelial venule PALS periarteriolar lymphoid sheath
HLA human leukocyte antigen (human MHC) PAMP pathogen-associated molecular pattern
HSP heat shock protein PAS periodic acid-Schiff (stain)
HUC histiocytic ulcerative colitis PCR polymerase chain reaction
IBD inflammatory bowel disease PCV packed cell volume (haematocrit)
ICAM-1 intercellular adhesion molecule 1 PHA phytohaemagglutinin (mitogen)
ICGN immune complex glomerulonephritis PIE pulmonary infiltration with eosinophilia
9